Cuproptosis is the most recently identi ed copper-dependent cell death form that in uences tricarboxylic acid (TCA) cycle. However, the relationship between cuproptosis and clinical prognosis, tumor microenvironment in ltration (TME), and response to immunotherapy remains unclear. Thus, we performed the following analysis. Single-sample gene-set enrichment analysis (ssGSEA) was employed to construct cuproptosisScore (cpS) and 1378 gastric cancer (GC) patients from ve independent public datasets were classi ed into high-or low-cpS groups according to the median of cpS. Then the impacts of cuproptosis on tumor microenvironment in ltration (TME), biological function, response to immunotherapy, and clinical prognosis of GC were evaluated. RiskScore and nomogram were constructed using Lasso Cox regression algorithm to validate its predictive capability in GC patients. Compared to patients with high cpS, patients with low cpS exhibited poorer prognosis, higher TNM stage, and stronger stromal activation. Meanwhile, the analysis of response to immunotherapy con rmed patients with high cpS could better bene t from immunotherapy and had a better susceptibility to chemotherapeutic drugs. 9 prognosis-related signatures were collected based on differentially expressed genes (DEGs) of cpS groups. Finally, a riskScore model was constructed using the multivariate Cox (multi-Cox) regression coe cients of prognosis-related signatures and had an excellent capability of predicting 1-, 3-, and 5-year survival in GC patients. In summary, this study revealed the role of curproptosis in TME, response to immunotherapy, and clinical prognosis in GC, which highlighted the signi cant clinical implications of curproptosis and provided novel ideas for the therapeutic application of cuproptosis in GC. associated with the inhibition of endometrial cancer and prostate cancer [11][12]. Thus, copper has a potentiality to be a new therapeutic target used to treatment of tumors by increasing intracellular copper accumulation [13][14]. Of note, the previous study of Tsvetkov et al indicated that intracellular copper accumulation could induce a novel cell death, termed cuproptosis, and it occurs by the direct binding of copper and lipoylated components of the tricarboxylic acid (TCA) cycle. Several cuproptosis-related genes (CRGs) were identi ed by Tsvetkov et al, which provides a new strategy for treatment and prognosis prediction of tumors [15]. Considering there have been no previous research about the effect of cuproptosis to GC in TME and prognosis, the correlation between cuproptosis and GC was explored in this study.Based on CRGs, we developed a cuproptosisScore (cpS) to explore the differences of tumor microenvironment in ltration (TME), biological function, response of immunotherapy, and clinical prognosis in different groups of GC. Then prognosis-related signatures were identi ed to further validate the effect of cuproptosis for predicting prognosis. We suggested that this study will lay a foundation for the therapeutic application of cuprop...

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BackgroundThe role of guanylate‐binding proteins (GBPs) in various cancers has been elucidated recently. However, our knowledge of the clinical relevance and biological characteristics of GBPs in hepatocellular carcinoma (HCC) remains limited.MethodsA total of 955 HCC patients were enrolled from five independent public HCC cohorts. The role of GBP molecules in HCC was preliminarily investigated, and a GBP family signature, termed GBPs‐score, was constructed by principal component analysis to combine the GBP molecule values. We revealed the effects of GBP genes and GBPs‐score in HCC via well‐established bioinformatics methods and validated GBP1‐5 experimentally in a tissue microarray (TMA) cohort.ResultsGBPs molecules were closely associated with the prognosis of patients with HCC, and a high GBPs‐score highly inferred a favorable survival outcome. We also revealed high GBPs‐score was related to anti‐tumor immunity, the immune‐hot tumor microenvironment (TME), and immunotherapy response. Among the GBPs members, GBP1‐5 rather than GBP6/7 may be dominant in these fields. The TMA analysis based on immunohistochemistry showed positive correlations between GBP1‐5 and the immune‐hot TME with abundant infiltration of CD8+ T cells in HCC.ConclusionsOur integrative study revealed the genetic and immunologic characterizations of GBPs in HCC and highlighted their potential values as promising biomarkers for prognosis and immunotherapy.

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Objective: To investigate the role of ferroptosis in Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal injury. Methods: GSE104954 and GSE108112 were retrieved from the GEO database and concatenated into one dataset. Expression of ferroptosis-related genes (FRGs) was extracted for differential analysis. The ferroptosis signature genes were identified by LASSO regression and SVM-RFE, and their differential expression levels and diagnostic efficacy were verified by independent data sets. The ceRNA (miRNA-TF-mRNA) regulatory network and clinical diagnostic model were constructed respectively. By using consensus clustering, ferroptosis subtypes were identified. ssGSEA and GSVA were employed to assess immune response and pathway activation. Pan-cancer genes were found in TCGA and GTEx. Differential expression of CD44 in was validated by qPCR and immunohistochemistry from HPA database. Results:Twenty-four FRGs were differentially expressed in patients with AAV kidney injury. Furthermore, five ferroptosis signature genes were identified by two machine learning algorithms. Not only were differentially expressed in independent datasets, the clinical diagnostic model constructed by these genes provided reference for clinical decision-making, but also the ceRNA network revealed their complex regulatory mechanisms. Unsupervised clustering analysis discovered two ferroptosis subtypes with distinct gene expression, immunological microenvironment, and biological functioning pathways. Notably, CD44 was found to be closely associated with many immune cells, most immune responses, and HLA genes, as well as prognosis, immune cell infiltration, TMB, and MSI in patients with a variety of tumors, suggesting it may be a potential intervention target for human diseases including AAV renal injury and tumors. Conclusions:Ferroptosis in AAV with renal injury is significantly correlated with the immunological microenvironment. For AAV with renal injury and tumors, CD44 could be a useful intervention target.

Background and study aim Chronic atrophic gastritis plays an important role in the process of gastric cancer. Deep learning is gradually introduced in the medical field, and how to better apply a convolutional neural network (CNN) to the diagnosis of chronic atrophic gastritis remains a research hotspot. This study was designed to improve the performance of CNN on diagnosing chronic atrophic gastritis by constructing and evaluating a network structure based on the characteristics of gastroscopic images. Methods Three endoscopists reviewed the endoscopic images of the gastric antrum from the Gastroscopy Image Database of Zhongnan Hospital and labelled available images according to pathological results. Two novel modules proposed recently were introduced to construct the Multi-scale with Attention net (MWA-net) considering the characters of similar medical images. After training the network using images of training sets, the diagnostic ability of the MWA-net was evaluated by comparing it with those of other deep learning models and endoscopists with varying degrees of expertise. Results As a result, 5,159 images of the gastric antrum from 2,240 patients were used to train and test the MWA-net. Compared with the direct application of famous networks, the MWA-net achieved the best performance (accuracy, 92.13%) with an increase of 1.80% compared to that of ResNet. The suspicious lesions indicated by the network are consistent with the conclusion of experts. The sensitivity and specificity of the convolutional network for gastric atrophy diagnosis are 90.19% and 94.51%, respectively, which are higher than those of experts. Conclusions Highly similar images of chronic atrophic gastritis can be identified by the proposed MWA-net, which has a better performance than other well-known networks. This work can further reduce the workload of gastroscopists, simplify the diagnostic process and provide medical assistance to more residents.

(1) Background: To assess whether the start time influences the outcomes of esophagogastroduodenoscopy (EGD). (2) Methods: We retrospectively analyzed the clinical data of patients who underwent EGD between January 2021 and December 2021 in our endoscopy center. The EGD were divided into three shifts, according to the start time. The lesion detection rate (LDR) and endoscopy biopsy rate (EBR) were used to evaluate the quality of the EGD. (3) Results: A total of 14,597 procedures were included in this study. The LDR of shift 2 was significantly lower than that of shift 1 (62.4% vs. 58.5%; p < 0.001). The EBR of shift 1 (37.4% vs. 31.5%; p < 0.001) and shift 3 (35.5% vs. 31.5%; p = 0.024) were significantly higher than that of shift 2; the EBR in shift 1 did not differ significantly from shift 3 (p = 0.280). The multivariable analysis for the EGD performed before 14:00 demonstrated a graded decrease in the LDR and EBR after adjusting the confounders (p < 0.001). (4) Conclusion: In a continuous working period, the lesion detection and biopsy submission of EGD are superior to those in the first three hours compared to the last three hours; the LDR and EBR decreased as the day progressed, probably due to the endoscopists’ fatigue.

Background and aims In endoscopic ultrasound (EUS)-fine-needle biopsy (FNB) of solid pancreatic mass lesions, the number of times the needle moves back and forth within the lesion might affect the collection of the sample and the subsequent diagnostic accuracy. Thus, this study was designed to compare the diagnostic adequacy between different numbers of back-and-forth movements in EUS-FNB. Methods Fifty-five patients with solid pancreatic masses underwent EUS-FNB sampling with the needle (22-gauge) moved 20 times (MTT) and 40 times (MFT) randomly and sequentially for a total of four alternating passes. We compared the acquisition rate of appropriate and adequate specimens for histologic assessment and diagnostic accuracy. Results Finally, 55 patients (35 men and 20 women) were included in the study. We found that 56.4% (31/55) and 60% (33/55) of the specimens obtained using MTT and MFT, respectively, could be adequately diagnosed histologically (P = 0.815, McNemar test). The diagnostic accuracy of MTT and MFT was 72.7% (40/55) and 80% (44/55), respectively (P = 0.289, McNemar test). The overall diagnostic accuracy was 89.1%. Conclusion There was no significant statistical difference between the histopathological diagnostic samples obtained in MTT and those obtained in MFT. Therefore, a large number of back-and-forth movements of the needle should be avoided during EUS-FNB, which can help reduce the operation time and may reduce the risk of intraoperative and postoperative complications (Clinical trial registration number: ChiCTR2000031106).